 Ph.D.
(1980) |
John
Frelinger
Professor of Microbiology & Immunology and of Oncology Primary Appointment: GEBS Cluster Affiliations: |
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| Contact Information: | ||
| University
of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642 |
Medical Center 2-3015 Phone: (585) 275-3405 Fax: (585) 461-4019 E-Mail: John_Frelinger@urmc.rochester.edu |
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- Research Focus
- Immunity to Tumor Antigens.
- Research Overview
- The paucity of animal models for prostate tumors has limited progress in the understanding and treatment of this cancer. We have begun a collaborative project to establish models of prostate cancer in mice so that we can address issues of immunological tolerance and immunotherapy strategies.
- The regulatory regions of PSA have been used to create a gene cassette that confers prostate-specific expression on two cloned genes in transgenic mice: the large T antigen of SV40 and human PSA. These mice will allow us to address the crucial issue of self-tolerance and how it may affect tumor immunity. It has become clear that tolerance is not absolute. We hypothesize that it may be possible to selectively direct an autoimmune response in an organ- or tissue-specific fashion. To examine this hypothesis, we will use transgenic mice which specifically express human PSA in the prostate, and investigate how this expression affects their ability to generate CTL responses to human PSA. These studies also will be performed using tumor cell lines that express PSA, as well as with tumors which develop spontaneously in the transgenic mice expressing large T antigen in the prostate. Further, by using HLA transgenic mice, we can investigate immune responses in systems with direct relevance to immunotherapy. The ultimate clinical use of these approaches will be to generate specific CTL that target a potentially dispensable organ, such as the prostate. These studies will also have implications for the treatment of other cancers and for our understanding of autoimmunity.
- Recent Publications
- Wei C, Callahan BP, Turner MJ, Willis RA, Lord EM, Barth RK, Frelinger JG Regulation of human prostate-specific antigen gene expression in transgenic mice: evidence for an enhancer between the PSA and human glandular kallikrein-1 genes. Int J Mol Med. 1998 Oct;2(4):487-96
- Santos K, Simon DA, Conway E, Bowers WJ, Mitra S, Foster TH, Lugade A, Lord EM, Federoff HJ, Dewhurst S, Frelinger JG. "Spatial and temporal expression of herpes simplex virus type 1 amplicon-encoded genes: implications for their use as immunization vectors." Hum Gene Ther. 2007 Feb;18(2):1-13.
- Malboeuf CM, Simon DA, Lee YE, Lankes HA, Dewhurst S, Frelinger JG, Rose RC. "Human papillomavirus-like particles mediate functional delivery of plasmid DNA to antigen presenting cells in vivo." Vaccine. 2007 Jan 22;
- Ramanayake T, Simon DA, Frelinger JG, Lord EM, Robert J. "In vivo study of T-cell responses to skin alloantigens in Xenopus using a novel whole-mount immunohistology method." Transplantation. 2007 Jan 27;83(2):159-66.
- Mitra S, Cassar SE, Niles DJ, Puskas JA, Frelinger JG, Foster TH "Photodynamic therapy mediates the oxygen-independent activation of hypoxia-inducible factor 1{alpha}." Mol Cancer Ther. 2006 Dec;5(12):3268-74
- Santos K, Duke CM, Rodriguez-Colon SM, Dakwar A, Fan S, Keefer MC, Federoff HJ, Frelinger JG, Bowers WJ, Dewhurst S "Effect of promoter strength on protein expression and immunogenicity of an HSV-1 amplicon vector encoding HIV-1 Gag." Vaccine. 2006 Nov 15;
- Gerber SA, Rybalko VY, Bigelow CE, Lugade AA, Foster TH, Frelinger JG, Lord EM "Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth." Am J Pathol. 2006 Nov;169(5):1739-52
- Wagner VE, Frelinger JG, Barth RK, Iglewski BH. "Quorum sensing: dynamic response of Pseudomonas aeruginosa to external signals." Trends Microbiol. 2006 Feb;14(2):55-8. Epub 2006 Jan 6.
- Lugade AA, Moran JP, et al. "Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor." J Immunol. 2005 Jun 15;174(12):7516-23.
- Gerber, S. A., M. J. Turner, et al. "Characterization of a lymph node within the mouse prostate: Detailed analysis using whole mount histology." Prostate 63(2): 105-16, 2005.
- Lugade, A. A., J. P. Moran, et al. "Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor." J Immunol 174(12): 7516-23, 2005.
- Mitra S, Goren EM, Frelinger JG, Foster TH. "Activation of heat shock protein 70 promoter with meso-tetrahydroxyphenyl chlorin photodynamic therapy reported by green fluorescent protein in vitro and in vivo." Photochem Photobiol. 78:615-22, 2003.
- Moran JP, Gerber SA, Martin CA, Frelinger JG, Lord EM. Transfection of the genes for interleukin-12 into the K1735 melanoma and the EMT6 mammary sarcoma murine cell lines reveals distinct mechanisms of antitumor activity. Int J Cancer. 106:690-8, 2003.
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